Microbial proteasomes as drug targets. Review uri icon

Overview

abstract

  • Proteasomes are compartmentalized, ATP-dependent, N-terminal nucleophile hydrolases that play essentials roles in intracellular protein turnover. They are present in all 3 kingdoms. Pharmacological inhibition of proteasomes is detrimental to cell viability. Proteasome inhibitor rugs revolutionize the treatment of multiple myeloma. Proteasomes in pathogenic microbes such as Mycobacterium tuberculosis (Mtb), Plasmodium falciparum (Pf), and other parasites and worms have been validated as therapeutic targets. Starting with Mtb proteasome, efforts in developing inhibitors selective for microbial proteasomes have made great progress lately. In this review, we describe the strategies and pharmacophores that have been used in developing proteasome inhibitors with potency and selectivity that spare human proteasomes and highlight the development of clinical proteasome inhibitor candidates for treatment of leishmaniasis and Chagas disease. Finally, we discuss the future challenges and therapeutical potentials of the microbial proteasome inhibitors.

publication date

  • December 9, 2021

Research

keywords

  • Chagas Disease
  • Leishmaniasis
  • Proteasome Endopeptidase Complex
  • Proteasome Inhibitors

Identity

PubMed Central ID

  • PMC8659679

Scopus Document Identifier

  • 85121333163

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2010.05.027

PubMed ID

  • 34882737

Additional Document Info

volume

  • 17

issue

  • 12